On October 3, 2015 the US government held the first of three public meetings to modernize federal regulations for genetically modified (GM) products. The last time the regulations were updated was in 1986, and with the advent of new GM technologies such as CRISPR/Cas, the system is in strong need of updating. Two of the main questions facing US federal agencies are: which agency is responsible for oversight, and should GM designation be based upon the end product or the process used. Currently gene editing techniques, such as CRISPR, that do not add foreign DNA are not considered GM and thus not subject to the GM regulations. Whether or not the definition of GM products will be expanded to include technologies such as CRISPR remains to be seen.

The CRISPR/Cas gene editing system is based upon an adaptive bacterial immune system against bacteriophages. To overcome this immune system, phages have evolved proteins that inhibit CRISPR/Cas systems. The mode of inhibition varies by type of Cas system targeted, but usually involves inhibiting the formation of the DNA-Cas complex. Anti-Cas proteins might find use in gene editing techniques by modulating the activity of the Cas complex.

DuPont Pioneer has entered into a partnership with Caribou Biosciences to share intellectual property rights for CRISPR/Cas gene editing in plants. Caribou Biosciences was founded by CRISPR researcher Jennifer Doudna to develop commercial uses of the CRISPR/Cas technology. This partnership enables sharing of intellectual property, but each company is limited in the plant species they may modify. DuPont Pioneer may use the technology to edit major crops like corn and soybean, while Caribou Biosciences will be limited to editing smaller market crops, such as fruits and vegetables.

Retinitis pigmentosa is an inherited disease that causes retina degradation, ultimately resulting in blindness. This disease has been well characterized, 90% of retinitis pigmentosa cases are the result of a single mutation in a single gene. Using skin cells from patients with this mutation, researchers were able to generate induced pluripotent stems cells and use CRISPR to correct the mutation. Researchers hope that these cells may one day be able to be grafted into a patient’s eye to restore sight, or at least slow the progression of the disease.

The journal Science has named CRISPR-Cas9 the “breakthrough of the year” due to its potential to revolutionize gene editing and gene therapy. This technology will allow scientist to study the relationship between genes and disease in a way never before possible.

Monkeys are an important model for studying human disease and developing drug therapies. However their use has been limited by the inability to produce specific genetic modifications. By using the CRISPR/Cas9 system Niu et al. were able selectively disrupt both PPAR-γ and RAG1 in the cynomolgus monkey (Macacafascicularis) with no off-target modifications detected, thus demonstrating that CRISPR/Cas9 technology could be used to further expand our knowledge of human disease through the use of monkey models.

Many human cancers are the result of chromosomal rearrangements which has made modeling certain cancers in mice challenging. Using CRISPR/Cas9 gene editing Maddalo et al. were able to induce chromosomal rearrangements similar to those found non-small cell lung cancers in mouse lung tissue. CRISPR/Cas9 modified mice developed lung tumors when compared to control mice demonstrating the capability of CRISPR/Cas9 technology to selectively edit mouse tissues to study human cancers.

Fatal hereditary diseases are potential targets for CRISPR/Cas9 gene therapies using homology directed repair. Using a mouse model for hereditary tyrosinemia type I – which causes liver damage and ultimately failure due to the buildup of toxic metabolites in the tyrosine catabolic pathway – d containing the same G to A point mutation found in the human form of the disease, Yin et al where able to repair the gene and reverse the associated phenotypes. While CRISPR/Cas9 gene editing has yet to be used to correct human genetic disease, results such as this provide a promising outlook for treatment of genetic diseases.

The dispute over who owns the CRISPR patents has triggered an outdated patent law known as an interference proceeding to determine the validity of the Broad Institutes patents. Interference proceedings were removed from patent disputes in 2013, however, since both the Broad Institutes and University of California-Berkely’s patents were filed prior to 2013 the dispute triggered what may be the last such proceeding. Interference proceedings resemble a court, a panel of three judges listen to oral arguments to determine who invented the technology first. Berkeley requested the interference proceeding after all the CRISPR patents were awarded to the Broad Institute. US patent law now uses a first to file and not first to invent criteria to settle disputes.